tbuckley/cabot-search huggingface dataset:
Receipt of Medications for Chronic Disease During the First 2 Years of the COVID-19 Pandemic Among Enrollees in Fee-for-Service Medicare
Authors: Nancy E. Morden, Weiping Zhou, Ziad Obermeyer, Jonathan Skinner
Journal: JAMA Network Open (2023)

Importance During the first 2 years of the COVID-19 pandemic, inpatient and ambulatory care declined dramatically. Little is known about prescription drug receipt during this period, particularly for populations with chronic illness and with high risk of adverse COVID-19 outcomes and decreased access to care. Objective To investigate whether receipt of medications was maintained during the first 2 years of the COVID-19 pandemic among older people with chronic diseases, particularly Asian, Black, and Hispanic populations and people with dementia, who faced pandemic-related care disruptions. Design, Setting, and Participants This cohort study used a 100% sample of US Medicare fee-for-service administrative data from 2019 to 2021 for community-dwelling beneficiaries aged 65 years or older. Population-based prescription fill rates were compared for 2020 and 2021 vs 2019. Data were analyzed from July 2022 to March 2023. Exposure The COVID-19 pandemic. Main Outcomes and Measures Age- and sex-adjusted monthly prescription fill rates were calculated for 5 groups of medications commonly prescribed for chronic disease : angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors (statins), oral diabetes medications, asthma and chronic obstructive pulmonary disease medications, and antidepressants. Measurements were stratified by race and ethnicity group and dementia diagnosis. Secondary analyses measured changes in the proportion of prescriptions dispensed as a 90-day or greater supply. Results Overall, the mean monthly cohort included 18 113 000 beneficiaries (mean [SD] age, 74.5 [7.4] years; 10 520 000 females [58.1%]; 587 000 Asian [3.2%], 1 069 000 Black [5.9%], 905 000 Hispanic [5.0%], and 14 929 000 White [82.4%]); 1 970 000 individuals (10.9%) were diagnosed with dementia. Across 5 drug classifications, mean fill rates increased by 2.07% (95% CI, 2.01% to 2.12%) in 2020 and decreased by 2.61% (95% CI, −2.67% to −2.56%) in 2021 compared with 2019. Fill rates decreased by less than the mean overall decrease for Black enrollees (−1.42%; 95% CI, −1.64% to −1.20%) and Asian enrollees (−1.05%; 95% CI, −1.36% to −0.77%) and people diagnosed with dementia (−0.38%; 95% CI, −0.54% to −0.23%). The proportion of fills dispensed as 90-day or greater supplies increased during the pandemic for all groups, with an increase per 100 fills of 3.98 fills (95% CI, 3.94 to 4.03 fills) overall. Conclusions and Relevance This study found that, in contrast to in-person health services, receipt of medications for chronic conditions was relatively stable in the first 2 years of the COVID-19 pandemic overall, across racial and ethnic groups, and for community-dwelling patients with dementia. This finding of stability may hold lessons for other outpatient services during the next pandemic.
Clinical and Biomarker Responses to <scp>BI</scp> 655064, an Antagonistic <scp>Anti‐CD40</scp> Antibody, in Patients With Active Lupus Nephritis: A Randomized, <scp>Double‐Blind</scp>, <scp>Placebo‐Controlled</scp>, Phase <scp>II</scp> Trial
Authors: David R. Jayne, Jürgen Steffgen, Juanita Romero‐Diaz, Ingeborg Bajema, Dimitrios T. Boumpas, Kajohnsak Noppakun, Hirofumi Amano, Harold Michael Gomez, Bancha Satirapoj, Yingyos Avihingsanon, Ratana Chawanasuntorapoj, Magdalena Madero, Beata Naumnik, Rhona Recto, Nora Fagan, Ivette Revollo, Jing Wu, Sudha Visvanathan, Richard Furie
Journal: Arthritis & Rheumatology (2023)

To characterize its dose-response relationship, BI 655064 (an anti-CD40 monoclonal antibody) was tested as an add-on to mycophenolate and glucocorticoids in patients with active lupus nephritis (LN).A total of 121 patients were randomized (2:1:1:2) to receive placebo or BI 655064 120, 180, or 240 mg and received a weekly loading dose for 3 weeks followed by dosing every 2 weeks for the 120 and 180 mg groups, and 120 mg weekly for the 240 mg group. The primary endpoint was complete renal response (CRR) at week 52. Secondary endpoints included CRR at week 26.A dose-response relationship with CRR at week 52 was not shown (BI 655064 120 mg, 38.3%; 180 mg, 45.0%; 240 mg, 44.6%; placebo, 48.3%). At week 26, 28.6% (120 mg), 50.0% (180 mg), 35.0% (240 mg), and 37.5% (placebo) achieved CRR. The unexpected high placebo response prompted a post hoc analysis evaluating confirmed CRR (cCRR, at weeks 46 and 52). cCRR was achieved in 22.5% (120 mg), 44.3% (180 mg), 38.2% (240 mg), and 29.1% (placebo) of patients. Most patients reported ≥1 adverse event (BI 655064, 85.7-95.0%; placebo, 97.5%), most frequently infections and infestations (BI 655064 61.9-75.0%; placebo 60%). Compared with other groups, higher rates of serious (20% vs. 7.5-10%) and severe infections (10% vs. 4.8-5.0%) were reported with 240 mg BI 655064.The trial failed to demonstrate a dose-response relationship for the primary CRR endpoint. Post hoc analyses suggest a potential benefit of BI 655064 180 mg in patients with active LN.
Errors in Figure 4
Authors: Hao Luo, Kenneth Man, Ian Wong
Journal: JAMA Psychiatry (2023)

Gyujoon Hwang, PhD; Junhao Wen, PhD; Susan Sotardi, MD; Edward S. Brodkin, MD; Ganesh B. Chand, PhD; Dominic B. Dwyer, PhD; Guray Erus, PhD; Jimit Doshi, MS; Pankhuri Singhal, BS; Dhivya Srinivasan, MS; Erdem Varol, PhD; Aristeidis Sotiras, PhD; Paola Dazzan, MD, PhD; Rene S. Kahn, MD, PhD; Hugo G. Schnack, PhD; Marcus V. Zanetti, PhD; Eva Meisenzahl, MD; Geraldo F. Busatto, PhD; Benedicto Crespo-Facorro, MD, PhD; Christos Pantelis, MD; Stephen J. Wood, PhD; Chuanjun Zhuo, MD, PhD; Russell T. Shinohara, PhD; Haochang Shou, PhD; Yong Fan, PhD; Adriana Di Martino, MD; Nikolaos Koutsouleris, MD; Raquel E. Gur, MD, PhD; Ruben C. Gur, PhD; Theodore D. Satterthwaite, MD; Daniel H. Wolf, MD, PhD; Christos Davatzikos, PhD
Rheumatoid Arthritis–Specific Autoimmunity in the Lung Before and at the Onset of Disease
Authors: Vijay Joshua, Malena Loberg Haarhaus, Aase Hensvold, Heidi Wähämaa, Christina Gerstner, Monika Hansson, Lena Israelsson, Ragnhild Stålesen, Magnus Sköld, Johan Grunewald, Lars Klareskog, Caroline Grönwall, Bence Réthi, Anca Catrina, Vivianne Malmström
Journal: Arthritis & Rheumatology (2023)

The lung is implicated as a site for breach of tolerance prior to onset of seropositive rheumatoid arthritis (RA). To substantiate this, we investigated lung-resident B cells in bronchoalveolar lavage (BAL) samples from untreated early RA patients and anti-citrullinated protein antibody (ACPA)-positive individuals at risk for developing RA.Single B cells (n = 7,680) were phenotyped and isolated from BAL samples from individuals at risk of RA (n = 3) and at RA diagnosis (n = 9). The immunoglobulin variable region transcripts were sequenced and selected for expression as monoclonal antibodies (n = 141). Monoclonal ACPAs were tested for reactivity patterns and binding to neutrophils.Using our single-cell approach, we found significantly increased proportions of B lymphocytes in ACPA+ compared to ACPA- individuals. Memory and double-negative B cells were prominent in all subgroups. Upon antibody re-expression, 7 highly mutated citrulline-autoreactive clones originating from different memory B cell subsets were identified, both in individuals at risk of RA and early RA patients. Lung IgG variable gene transcripts from ACPA+ individuals carried frequent mutation-induced N-linked Fab glycosylation sites (P < 0.001), often in the framework 3 of the variable region. Two of the lung ACPAs bound to activated neutrophils, 1 from an individual at risk of RA and 1 from an early RA patient.T cell-driven B cell differentiation resulting in local class switching and somatic hypermutation are evident in lungs before as well as in early stages of ACPA+ RA. Our findings add to the notion of lung mucosa being a site for initiation of citrulline autoimmunity preceding seropositive RA.
Repurposing clinically available drugs and therapies for pathogenic targets to combat SARS‐CoV‐2
Authors: Yiying Xue, Husheng Mei, Yisa Chen, James D. Griffin, Qingsong Liu, Ellen Weisberg, Jing Yang
Journal: MedComm (2023)

The coronavirus disease 2019 (COVID-19) pandemic has affected a large portion of the global population, both physically and mentally. Current evidence suggests that the rapidly evolving coronavirus subvariants risk rendering vaccines and antibodies ineffective due to their potential to evade existing immunity, with enhanced transmission activity and higher reinfection rates that could lead to new outbreaks across the globe. The goal of viral management is to disrupt the viral life cycle as well as to relieve severe symptoms such as lung damage, cytokine storm, and organ failure. In the fight against viruses, the combination of viral genome sequencing, elucidation of the structure of viral proteins, and identifying proteins that are highly conserved across multiple coronaviruses has revealed many potential molecular targets. In addition, the time- and cost-effective repurposing of preexisting antiviral drugs or approved/clinical drugs for these targets offers considerable clinical advantages for COVID-19 patients. This review provides a comprehensive overview of various identified pathogenic targets and pathways as well as corresponding repurposed approved/clinical drugs and their potential against COVID-19. These findings provide new insight into the discovery of novel therapeutic strategies that could be applied to the control of disease symptoms emanating from evolving SARS-CoV-2 variants.
Caecilian Genomes Reveal the Molecular Basis of Adaptation and Convergent Evolution of Limblessness in Snakes and Caecilians
Authors: Vladimir Ovchinnikov, Marcela Uliano-Silva, Mark Wilkinson, Jonathan Wood, Michelle Smith, Karen Oliver, Ying Sims, James Torrance, Alexander Suh, Shane A McCarthy, Richard Durbin, Mary J O’Connell
Journal: Molecular Biology and Evolution (2023)

Abstract We present genome sequences for the caecilians Geotrypetes seraphini (3.8 Gb) and Microcaecilia unicolor (4.7 Gb), representatives of a limbless, mostly soil-dwelling amphibian clade with reduced eyes, and unique putatively chemosensory tentacles. More than 69% of both genomes are composed of repeats, with retrotransposons being the most abundant. We identify 1,150 orthogroups that are unique to caecilians and enriched for functions in olfaction and detection of chemical signals. There are 379 orthogroups with signatures of positive selection on caecilian lineages with roles in organ development and morphogenesis, sensory perception, and immunity amongst others. We discover that caecilian genomes are missing the zone of polarizing activity regulatorysequence (ZRS) enhancer of Sonic Hedgehog which is also mutated in snakes. In vivo deletions have shown ZRS is required for limb development in mice, thus, revealing a shared molecular target implicated in the independent evolution of limblessness in snakes and caecilians.
Relationship between BCL2 mutations and follicular lymphoma outcome in the chemoimmunotherapy era
Authors: Cristina Correia, Matthew J. Maurer, Samantha J. McDonough, Paula A. Schneider, Paige E. Ross, Anne J. Novak, Andrew L. Feldman, James R. Cerhan, Susan L. Slager, Thomas E. Witzig, Bruce W. Eckloff, Hu Li, Grzegorz S. Nowakowski, Scott H. Kaufmann
Journal: Blood Cancer Journal (2023)

How to identify follicular lymphoma (FL) patients with low disease burden but high risk for early progression is unclear. Building on a prior study demonstrating the early transformation of FLs with high variant allele frequency (VAF) BCL2 mutations at activation-induced cytidine deaminase (AICDA) sites, we examined 11 AICDA mutational targets, including BCL2, BCL6, PAX5, PIM1, RHOH, SOCS, and MYC, in 199 newly diagnosed grade 1 and 2 FLs. BCL2 mutations with VAF ≥20% occurred in 52% of cases. Among 97 FL patients who did not initially receive rituximab-containing therapy, nonsynonymous BCL2 mutations at VAF ≥20% were associated with increased transformation risk (HR 3.01, 95% CI 1.04-8.78, p = 0.043) and a trend toward shorter event-free survival (EFS, median 20 months with mutations versus 54 months without, p = 0.052). Other sequenced genes were less frequently mutated and did not increase the prognostic value of the panel. Across the entire population, nonsynonymous BCL2 mutations at VAF ≥20% were associated with decreased EFS (HR 1.55, 95% CI 1.02-2.35, p = 0.043 after correction for FLIPI and treatment) and decreased overall survival after median 14-year follow-up (HR 1.82, 95% CI 1.05-3.17, p = 0.034). Thus, high VAF nonsynonymous BCL2 mutations remain prognostic even in the chemoimmunotherapy era.
Efficacy and Safety of the <scp>TYK2</scp>/<scp>JAK1</scp> Inhibitor Brepocitinib for Active Psoriatic Arthritis: A Phase <scp>IIb</scp> Randomized Controlled Trial
Authors: Philip Mease, Philip Helliwell, Paula Silwinska‐Stanczyk, Malgorzata Miakisz, Andrew Ostor, Elena Peeva, Michael S. Vincent, Qiankun Sun, Vanja Sikirica, Randall Winnette, Ruolun Qiu, Gang Li, Gang Feng, Jean S. Beebe, David A. Martin
Journal: Arthritis & Rheumatology (2023)

Brepocitinib is a TYK2/JAK1 inhibitor in development for the treatment of several immunologic diseases. The efficacy and safety of oral brepocitinib were assessed in participants with moderately-to-severely active psoriatic arthritis (PsA) for up to 52 weeks.In this placebo-controlled, dose-ranging, phase IIb study, participants were randomized to receive 10 mg, 30 mg, or 60 mg of brepocitinib once daily or placebo, advancing to 30 mg or 60 mg of brepocitinib once daily at week 16. The primary endpoint was the response rate according to the American College of Rheumatology criteria for 20% improvement (ACR20) in disease activity at week 16. Secondary endpoints included response rates according to the ACR50/ACR70 response criteria, 75% and 90% improvement in the Psoriasis Area and Severity Index (PASI75/PASI90) score, and minimal disease activity (MDA) at weeks 16 and 52. Adverse events were monitored throughout the study.Overall, 218 participants were randomized and treated. At week 16, the brepocitinib 30 mg and 60 mg once daily groups had significantly greater ACR20 response rates (66.7% [P = 0.0197] and 74.6% [P = 0.0006], respectively), versus the placebo group (43.3%), and significantly higher ACR50/ACR70, PASI75/PASI90, and MDA response rates. Response rates were maintained or improved through week 52. Adverse events were mostly mild/moderate; serious adverse events (15) in 12 participants (5.5%) included infections in 6 participants (2.8%) in the brepocitinib 30 mg and 60 mg once daily groups. No major adverse cardiovascular events or deaths occurred.Treatment with brepocitinib at dosages of 30 mg and 60 mg once daily was superior to placebo at reducing signs and symptoms of PsA. Brepocitinib was generally well tolerated throughout the 52-week study, with a safety profile consistent with those found in other brepocitinib clinical trials.
Correction: Combined inhibition of BCL-2 and MCL-1 overcomes BAX deficiency-mediated resistance of TP53-mutant acute myeloid leukemia to individual BH3 mimetics
Authors: Bing Z. Carter, Po Yee Mak, Wenjing Tao, Edward Ayoub, Lauren B. Ostermann, Xuelin Huang, Sanam Loghavi, Steffen Boettcher, Yuki Nishida, Vivian Ruvolo, Paul E. Hughes, Phuong K. Morrow, Torsten Haferlach, Steven Kornblau, Muharrem Muftuoglu, Michael Andreeff
Journal: Blood Cancer Journal (2023)
Three-row versus two-row circular staplers for left-sided colorectal anastomosis: a propensity score-matched analysis of the iCral 2 and 3 prospective cohorts
Authors: Marco Catarci, Stefano Guadagni, Francesco Masedu, Giacomo Ruffo, Massimo Giuseppe Viola, Felice Borghi, Gianandrea Baldazzi, Marco Scatizzi
Journal: International Journal of Surgery (2023)

Since most anastomoses after left-sided colorectal resections are performed with a circular stapler, any technological change in stapling devices may influence the incidence of anastomotic adverse events. The aim of the present study was to analyze the effect of a three-row circular stapler on anastomotic leakage and related morbidity after left-sided colorectal resections.
The mTOR Signaling Pathway Interacts with the ER Stress Response and the Unfolded Protein Response in Cancer
Authors: Sahar Mafi, Elham Ahmadi, Eileen Meehan, Conner Chiari, Behzad Mansoori, Hossein Sadeghi, Sahar Milani, Morteza Jafarinia, Shahram Taeb, Bayan Mafakheri Bashmagh, Seyed Mohammad Ali Mansoorian, Mohammad Sadegh Soltani-Zangbar, Kepeng Wang, Davoud Rostamzadeh
Journal: Cancer Research (2023)

The mTOR complex 1 (mTORC1) coordinates several important environmental and intracellular cues to control a variety of biological processes, such as cell growth, survival, autophagy, and metabolism, in response to energy levels, growth signals, and nutrients. The endoplasmic reticulum (ER) is a crucial intracellular organelle that is essential for numerous cellular functions, including the synthesis, folding, and modification of newly synthesized proteins, stress responsiveness, and maintainence of cellular homeostasis. mTOR-mediated upregulation of protein synthesis induces the accumulation of misfolded or unfolded proteins in the ER lumen, which induces ER stress, leading to activation of the unfolded protein response (UPR) pathway. Reciprocally, ER stress regulates the PI3K/AKT/mTOR signaling pathway. Therefore, under pathologic conditions, the cross-talk between the mTOR and UPR signaling pathways during cellular stress can critically affect cancer cell fate and may be involved in the pathogenesis and therapeutic outcome of cancer. Here, we discuss accumulating evidence showing the mechanism of action, interconnections, and molecular links between mTOR signaling and ER stress in tumorigenesis and highlights potential therapeutic implications for numerous cancers.
Celebrating a breakthrough: the first-ever FDA-approved treatment for geographic atrophy: a correspondence
Authors: Abdul Moiz Khan, Syeda Shahnoor, Hareem Khan, Marium Affendi, Sawsane Ahmad Ghaddar
Journal: International Journal of Surgery (2023)

Khan, Abdul Moiz MBBS; Khan, Hareem MBBS; Affendi, Marium MBBS; Shahnoor, Syeda MBBS; Ghaddar, Sawsane Ahmad MD Author Information
MEK Inhibition Sensitizes Pancreatic Cancer to STING Agonism by Tumor Cell–intrinsic Amplification of Type I IFN Signaling
Authors: Razmik Ghukasyan, Keke Liang, Kevin Chau, Luyi Li, Charlotte Chan, Evan R. Abt, Thuc Le, Joon Y. Park, Nanping Wu, Alykhan Premji, Robert Damoiseaux, Tony Luu, Amanda Labora, Khalid Rashid, Jason M. Link, Caius G. Radu, Timothy R. Donahue
Journal: Clinical Cancer Research (2023)

Stimulator of interferon genes (STING) agonists are currently in development for treatment of solid tumors, including pancreatic ductal adenocarcinoma (PDAC). Response rates to STING agonists alone have been promising yet modest, and combination therapies will likely be required to elicit their full potency. We sought to identify combination therapies and mechanisms that augment the tumor cell-intrinsic effect of therapeutically relevant STING agonists apart from their known effects on tumor immunity.
Sinus inflammation and chronic rhinosinusitis are associated with a diagnosis of new onset asthma in the following year
Authors: Brian S. Schwartz, Jonathan S. Pollak, Karen Bandeen‐Roche, Annemarie G. Hirsch, Ashton E. Lehmann, Robert C. Kern, Bruce K. Tan, Atsushi Kato, Robert P. Schleimer, Anju T. Peters
Journal: Allergy (2023)

Abstract Background Chronic rhinosinusitis (CRS) and asthma commonly co‐occur. No studies have leveraged large samples needed to formally address whether preexisting CRS is associated with new onset asthma over time. Methods We evaluated whether prevalent CRS [identified in two ways: validated text algorithm applied to sinus computerized tomography (CT) scan or two diagnoses] was associated with new onset adult asthma in the following year. We used electronic health record data from Geisinger from 2008 to 2019. For each year we removed persons with any evidence of asthma through the end of the year, then identified those with new diagnosis of asthma in the following year. Complementary log–log regression was used to adjust for confounding variables (e.g., sociodemographic, contact with the health system, comorbidities), and hazard ratios (HRs) and 95% confidence intervals (CI) were calculated. Results A total of 35,441 persons were diagnosed with new onset asthma and were compared to 890,956 persons who did not develop asthma. Persons with new onset asthma tended to be female (69.6%) and younger (mean [SD] age 45.9 [17.0] years). Both CRS definitions were associated (HR, 95% CI) with new onset asthma, with 2.21 (1.93, 2.54) and 1.48 (1.38, 1.59) for CRS based on sinus CT scan and two diagnoses, respectively. New onset asthma was uncommonly observed in persons with a history of sinus surgery. Conclusion Prevalent CRS identified with two complementary approaches was associated with a diagnosis of new onset asthma in the following year. The findings may have clinical implications for the prevention of asthma.
Gamma Activity and Connectivity Increased in Patients’ Brains Before Death
Authors: Emily Harris
Journal: JAMA (2023)

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Determining the Power Required for Comparing Lobectomy vs Total Thyroidectomy for Papillary Thyroid Carcinoma—Reply
Authors: Siyuan Xu, Shaoyan Liu, Jie Liu
Journal: JAMA Surgery (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal